# US 10,501,536 B2 · Anti-IL-33 antibodies and uses thereof for disease treatment

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- Number: US 10,501,536 B2
- Document ID: US10501536B2
- Status: Granted
- Kind: B2
- Application number: 15/791,641
- Filed: 2017-10-24
- Published: 2018-05-03
- Granted: 2019-12-10
- Earliest claimed: 2016-10-28
- Assignees: Eli Lilly and Company
- Applicants: Eli Lilly and Company
- Inventors: Robert Jan Benschop; Julian Davies; Angela Jeannine Okragly; Chetankumar Natvarlal Patel; Stephanie Marie Truhlar
- Web page: https://patentgrep.com/patent/US10501536B2

## CPC

- C07K 16/244: {Interleukins [IL]}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Antibodies which bind and neutralize human IL-33, and methods of using same, are provided, said antibodies are useful as agents for treating conditions associated with allergic disease including treating atopic dermatitis.

## Claims

### Claim 1

An antibody that binds human IL-33, comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, and wherein the amino acid sequence of LCDR1 is SEQ ID NO: 16, the amino acid sequence of LCDR2 is SEQ ID NO: 17, the amino acid sequence of LCDR3 is SEQ ID NO: 18, the amino acid sequence of HCDR1 is SEQ ID NO: 13, the amino acid sequence of HCDR2 is SEQ ID NO: 14, and the amino acid sequence of HCDR3 is SEQ ID NO: 15, and wherein Xaa at position 6 of SEQ ID NO: 13 is Ser or Phe, Xaa at position 2 of SEQ ID NO: 15 is Leu or Ile, Xaa at position 6 of SEQ ID NO: 17 is Ala or Leu, and Xaa at position 6 of SEQ ID NO: 18 is Ser or Pro.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein:
a. Xaa at position 6 of SEQ ID NO: 13 is Ser;
b. Xaa at position 2 of SEQ ID NO: 15 is Leu;
c. Xaa at position 6 of SEQ ID NO: 17 is Ala; and
d. Xaa at position 6 of SEQ ID NO: 18 is Ser.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein:
a. Xaa at position 6 of SEQ ID NO: 13 is Phe;
b. Xaa at position 2 of SEQ ID NO: 15 is Leu;
c. Xaa at position 6 of SEQ ID NO: 17 is Leu; and
d. Xaa at position 6 of SEQ ID NO: 18 is Pro.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein:
a. Xaa at position 6 of SEQ ID NO: 13 is Phe;
b. Xaa at position 2 of SEQ ID NO: 15 is Ile;
c. Xaa at position 6 of SEQ ID NO: 17 is Leu; and
d. Xaa at position 6 of SEQ ID NO: 18 is Pro.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein the amino acid sequence of the LCVR is SEQ ID NO: 4, SEQ ID NO: 8, or SEQ ID NO: 12, and the amino acid sequence of the HCVR is SEQ ID NO: 3, SEQ ID NO: 7, or SEQ ID NO: 11.

### Claim 6 (depends on 5)

The antibody of claim 5, wherein the amino acid sequence of the LCVR is SEQ ID NO: 4, and the amino acid sequence of the HCVR is SEQ ID NO: 3.

### Claim 7 (depends on 5)

The antibody of claim 5, wherein the amino acid sequence of the LCVR is SEQ ID NO: 8, and the amino acid sequence of the HCVR is SEQ ID NO: 7.

### Claim 8 (depends on 5)

The antibody of claim 5, wherein the amino acid sequence of the LCVR is SEQ ID NO: 12, and the amino acid sequence of the HCVR is SEQ ID NO: 11.

### Claim 9 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a light chain (LC) and a heavy chain (HC), and wherein the amino acid sequence of the LC is SEQ ID NO: 2, SEQ ID NO: 6, or SEQ ID NO: 10, and the amino acid sequence of the HC is SEQ ID NO: 1, SEQ ID NO: 5, or SEQ ID NO: 9.

### Claim 10 (depends on 9)

The antibody of claim 9, wherein the amino acid sequence of the LC is SEQ ID NO: 2, and the amino acid sequence of the HC is SEQ ID NO: 1.

### Claim 11 (depends on 9)

The antibody of claim 9, wherein the amino acid sequence of the LC is SEQ ID NO: 6, and the amino acid sequence of the HC is SEQ ID NO: 5.

### Claim 12 (depends on 9)

The antibody of claim 9, wherein the amino acid sequence of the LC is SEQ ID NO: 10, and the amino acid sequence of the HC is SEQ ID NO: 9.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising the antibody of claim 1, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

### Claim 14 (depends on 1)

A method of treating one or more allergic disease, comprising administering to a patient in need thereof an effective amount of the antibody of claim 1.

### Claim 15 (depends on 14)

The method of claim 14, wherein the allergic disease is atopic dermatitis, asthma, allergic rhinitis, or food allergy.

### Claim 16 (depends on 1)

A method of treating atopic dermatitis, comprising administering to a patient in need thereof an effective amount of the antibody of claim 1.

### Claim 17 (depends on 1)

A method of treating at least one of eosinophilic esophagitis, scleroderma/systemic sclerosis, ulcerative colitis, and chronic obstructive pulmonary disease, comprising administering to a patient in need thereof an effective amount of the antibody of claim 1.